Page 19 - ASME_NEMB_2016_Program

TRACK 1 Technical Program

tion and higher order simplified spherical harmonics approximation to the Li, Yushen Jin and Zhifei Dai, Nanohybrid liposomal cerasomes with good
radiative transport equation (RTE). Regardless of reconstruction approach, physiological stability and rapid temperature responsiveness for HIFU trig-
the results show that while frequency-domain measurements may result in gered local chemotherapy of cancer, ACS Nano, 2015, 9, 1280-1293.
superior image reconstructions over CW measurements, data acquisition 2)Lijia Jing, Jiyun Shi, Yaqian Li, Di Fan, Renfa Liu, Zhifei Dai, Fan Wang, Jie
times were significantly longer, limiting utility for small animal imaging. Herein Tian, 177Lu -Labeled Cerasomes Encapsulating Indocyanine Green for Can-
we demonstrate the adaptation of recently available CMOS detectors that cer Theranostics, ACS Applied Materials & Interfaces, 2015, in press.
can mitigate acquisition rates while maintaining signal to noise ratios that are 3)Xiaolong Liang, Xiaoda Li, Xiuli Yue, Zhifei Dai, Conjugation of porphyrin
needed for robust image reconstruction for far-red and near-infrared fluores- to nanohybrid cerasomes for photodynamic therapy of cancer, Angewandte
cence tomography in small animals. Our next steps are to track cancer me- Chemie International Edition, 2011, 50-11622-11627.
tastases in 3D with far-red fluorescent gene reporters and with near-infrared
nano- and antibody-based probes that target cancer. 10:00am Leukocyte-based Biomimetic Nanovesicles for the Im-
aging of Inflamed Vasculature
TUESDAY, FEBRUARY, 23 Technical Presentation. NEMB2016-6049

Jonathan Martinez, Roberto Molinaro, Naama Toledano Furman,
1-4 Michael Evangelopoulos, Enrica De Rosa, Houston Methodist Re-
NOVEL NANOPARTICLES FOR IMAGING, DIAGNOSTICS, AND search Institute, Houston, TX, United States, Roman Sukhovershin,
THERAPY Methodist Research Institute, Houston, TX, United States, Kelly A
Hartman, John P. Cooke, Houston Methodist Research Institute,
Houston, TX, United States, Ennio Tasciotti, The Methodist Hospi-
Sam Houston 9:30am - 11:00am tal Research Institute, Houston, TX, United States

Session Organizer: Jie Zheng, The University of Texas at Dallas, Uncontrolled inflammation plays a significant role in the establishment and
Richardson, TX, United States progression of the cancer lesion. Specific probes that can provide detailed
information on the location, extent and duration of the inflammatory pro-
cess hold promise to improve the treatment of these disorders. Targeted
9:30am Nanohybrid Liposomal Cerasome for Imaging Guided nanoparticles offer great advantages for diagnostic imaging, however their
Cancer Therapy sequestration by the mononuclear phagocyte system and inability to ad-
equately negotiate other biological barriers has hindered their targeting,
Keynote. NEMB2016-6079 increased their toxicity, and limited their clinical success. Here we present a
new biomimetic approach able to address these limitations. We developed
Zhifei Dai, Peking University, Beijing, China Cell-derived Biomimetic Nanovesicles (CBN) composed by plasma mem-
brane proteins (derived from leukocytes), and incorporated into a liposomal
Both liposomes and silica nanoparticles (NPs) have been widely investigated bilayer. This method allowed the transfer of 200 distinct membrane asso-
in the field of medicine. However, the serious drawbacks of silica NPs are ciated proteins to the surface of the CBN. The CBN showed the traditional
their inherently non-biodegradability, high rigidity and low biocompatibility. physicochemical features of liposomes, and their ability to load diverse
Despite the excellent biocompatibility, liposomes still have not attained their payloads (e.g., hydrophilic, amphiphilic, and hydrophobic). In addition, the
full potential as drug and gene delivery vehicles due to the insufficient mor- CBN exhibited preferential docking and firm adhesion onto TNF-α activated
phological stability. Therefore, we developed a cerasome with a liposomal (i.e., inflamed) endothelia. Furthermore, when systemically administrated,
bilayer structure and an atomic layer of polyorganosiloxane networks on its the incorporation of leukocyte self tolerance membrane proteins (CD47,
surface by molecularly designed lipidic organoalkoxysilane. Such unique CD45), enabled the CBN to exhibit longer circulation time and delayed the
structure gives wide applicability to cerasomes in roles as drug and gene sequestration by the mononuclear phagocyte system. The CBN represents
delivery systems. a platform that successfully combined the unique features of liposomes with
leukocyte-like characteristics to develop a novel delivery platform that fuses
Cerasome combines the advantages of both conventional liposomes and nanotechnology with membrane biology.
silica NPs: (1) The siloxane surface can facilitate the stabilization of cera-
somes in an environment with a slightly alkaline pH or a significant salt The ability of CBN to target inflamed vasculature in vivo was tested using
concentration; (2) The presence of a liposomal bilayer structure reduces three distinct models of localized tissue inflammation, cancer lesion, and
the overall rigidity and density of cerasomes greatly compared to silica NPs; atherosclerotic plaque. We used high-speed intravital microscopy (IVM) to
(3) Cerasomes can be loaded with hydrophilic, hydrophobic as well as am- evaluate flow dynamics, biodistribution, targeting and tissue accumulation.
phiphilic drugs and imaging agents without destroying their morphological We established a local inflammatory site using a single injection of lipopoly-
stability; (5) The silanol groups on the surface of cerasome can be function- saccharide in the ears of the mice. IVM analysis revealed that CBN target-
alized to allow the easy bioconjugation of biomolecules with silane-coupler ed inflamed vessels within the ear at a 10-fold higher concentration than
chemistry. liposomes. Using syngeneic models of breast cancer and melanoma, we
observed CBN targeting and adhering to cancer vessels within the first 30
Various therapeutic agents (doxorubicin, paclitaxel, siRNA and radionuclides minutes after systemic administration, followed by substantial extravasation
etc.) and imaging agents (radionuclides, quantum dots, gold and Fe O 4 in the perivascular region by 24 hours. In addition, we observed minimal
3
etc.) were loaded into cersomes. Moreover, their surface was outfitted with accumulation in the liver and spleen of CBN whereas liposomes displayed
ligands for targeting delivery to the tumor sites. Each component would negligible tumor accumulation and were predominately sequestered in the
operate a different function, such as molecular targeting, contrast enhanced liver and spleen. Atherosclerosis was induced in apolipoprotein E-deficient
imaging (fluorescence, PET, MRI, CT, photoacoustic and ultrasound etc.) and (apoE-/-) mice fed on a high-fat diet for 4 months and then injected intrave-
therapy (chemotherapy, radiotherapy, photothermal therapy, photodynamic nously with CBN. After 1 hour, CBN were surrounding each atherosclerotic
therapy, gene therapy or combined therapy). Therefore, the cerasomes plaque of the aorta. In addition to using optical imaging to evaluate the
serve as a theranostic nanomedicine to be capable of noninvasive imaging location of the inflammatory lesion, the versatility of CBN permits the load-
and remote-controlled therapy. ing of contrast agents to enable magnetic resonance imaging, ultrasound,
computed tomography, and radioisotope imaging. As a matter of fact after 19
-1 -1
References incorporation with gadolinium, CBN exhibited r2 relaxivities >>40 mM s , a
1)Xiaolong Liang, Jing Gao, Lingdong Jiang, Jianwen Luo, Lijia Jing, Xiaoda significant increase compared to gadolinium-based contrast agents in the